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However, the molecular mechanism of this process is not fully understood. We hypothesize that the antifibrotic effects of <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\u2010dependent kinase I (<jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content>) are mediated via regulation of the <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 signalling pathway, both via <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and the Smad\u2010dependent route. Kidney fibrosis was induced by unilateral ureter obstruction (<jats:styled-content style=\"fixed-case\">UUO<\/jats:styled-content>) in wild\u2010type and <jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content>\u2010deficient (<jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice. The <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content> signalling pathway was activated by application of the soluble guanylate cyclase (<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>) stimulator <jats:styled-content style=\"fixed-case\">BAY<\/jats:styled-content> 41\u20108543 (<jats:styled-content style=\"fixed-case\">BAY<\/jats:styled-content>), beginning 1 day after <jats:styled-content style=\"fixed-case\">UUO<\/jats:styled-content>. After 7 days, the antifibrotic effects of <jats:styled-content style=\"fixed-case\">BAY<\/jats:styled-content> were analysed by measuring <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression of characteristic fibrotic biomarkers. The effects of <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 on cultured fibroblasts were also analysed <jats:italic>in vitro<\/jats:italic>. <jats:styled-content style=\"fixed-case\">BAY<\/jats:styled-content> application influenced the activity of the extracellular matrix (<jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content>)\u2010degrading matrix metalloproteases (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>9) and their inhibitor tissue inhibitors of metalloproteinase\u20101, the secretion of cytokines (e.g. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106) and the expression pattern of ECM proteins (e.g. collagen, fibronectin) and profibrotic mediators (e.g. connective tissue growth factors and plasminogen\u2010activator inhibitor\u20101). Activation of the <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content> signalling pathway showed protective effects against fibrosis which were mediated by inhibition of P\u2010Erk1\/2 and translocation of P\u2010smad3. The elucidation of these signalling mechanisms might support the development of new therapeutic options regarding <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGKI<\/jats:styled-content>\u2010mediated antifibrotic actions.<\/jats:p>","DOI":"10.1002\/2211-5463.12202","type":"journal-article","created":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T13:53:31Z","timestamp":1485957211000},"page":"550-561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Inhibition of the <scp>TGF<\/scp>\u03b2 signalling pathway by <scp>cGMP<\/scp> and <scp>cGMP<\/scp>\u2010dependent kinase I in renal fibrosis"],"prefix":"10.1002","volume":"7","author":[{"given":"Elisabeth","family":"Schinner","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Regensburg 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